Modeling senecavirus a replication in immortalized porcine alveolar macrophages triggers a robust interferon-mediated immune response that conversely constrains viral replication

Senecavirus A (SVA) is a newly emerging causative agent of vesicular diseases in swine characterized with wide genetic diversity and rapid evolution. The lack of immunologically active cell culture model impedes the study of SVA-specific innate immunity. Here, an immortalized porcine alveolar macrophages 3D4/21 strongly and productively supported replication of two SVA strains. To elaborate global and dynamic host immune response, we demonstrated that 3D4/21 intrinsically expressed canonical ISGs which were important for pre-empting viral infection. Moreover, 3D4/21 were constitutively abundant in RIG-I-like receptors (RLRs) RIG-I and MDA5 necessary for sensing RNA virus infection, thereby enabling 3D4/21 cells to establish persistent and efficient antiviral status, in particular the most dramatic and sustained expression of type I/II interferons and inflammatory and innate immune genes critical for constraining SVA replication. Our study reveals a pivotal regulatory connection between virus and host that points to the SVA pathogenesis and potential vaccine development.

Automated summary

Senecavirus A (SVA) is a newly emerged pathogen that causes vesicular diseases in swine with wide genetic diversity and rapid evolution. In this study, an immortalized porcine alveolar macrophage cell line (3D4/21) was found to support productive replication of SVA strains and exhibit innate immune response against SVA infection. The activation of RIG-I-like receptors in 3D4/21 cells leads to sustained expression of interferons and innate immune genes critical for constraining SVA replication.